Haploid loss of ID4 in Eμ-TCL1-tg mice leads to accelerated CLL disease progression. (A) ID4 protein expression in CD19⁺-selected B cells from Eμ-TCL1-tg mice without (+/+) or with (+/−) haploid loss of ID4. Numbers at the bottom give the relative amounts of ID4 protein. (B) Left: WBC counts from blood smears obtained from mice aged from 2 to 8 months. Right: 100 μL of peripheral blood lymphocytes (PBL) were collected each month and measured by flow cytometry for the percentage of CD19⁺CD5⁺ cells in mice aged from 9 to 13 months. Bottom: Number of live animals from each group that was available and analyzed. *Indicates statistically significant differences based on 2-sample t tests. (C) Representative blood smear stained with Wright-Giemsa showing an increased number of circulating lymphocytes in Eμ-TCL1-tg mice with haploid loss of ID4 (age, 14 months), but not in age-matched control heterozygous ID4 mice. (D) Kaplan-Meier survival curves from F1 littermates of Eμ-TCL1-tg mice with or without the haploid loss of ID4. (E) Histologic immunophenotyping of spleen, liver, and brain from Eμ-TCL1 mice with haploid loss of ID4. Top: Obliterative lymphoma is present in the periarteriolar lymphoid sheaths (white pulp) of spleen. Middle: Evidence of lymphocyte infiltration is suggested in approximately 25% of the liver sections by intrasinusoidal neoplastic cells. Bottom: Marked hippocampal neuronal necrosis was observed in the section from brain, as well as moderate multifocal cerebral, cerebellar, and meningeal hemorrhage, indicating the infiltration of malignant lymphocytes in the brain.